The role of epidermal growth factor (EGF) and its receptors (EGF-R) during embryonic development and during the differentiation and loss of tumorigenicity of teratocarcinoma cells will be studied. Epidermal growth factor receptors have been demonstrated on the cell surface of certain differentiated teratocarcinoma cell lines. Undifferentiated embryonal carcinoma (EC) cells are malignant and totipotent, but their differentiated cell products have little or no tumorigenicity. The former cells do not have significant numbers of 125I-EGF binding sites and the hypothesis is that in the teratocarcinoma system, growth control may be governed by EGF and its receptors (EGF-R). In many respects, teratocarcinoma cells are a model of mouse development, and this suggests that the tissues of the mouse may become subject to growth control during development either by a) the appearance of EGF-R and maternal EGF or by b) the synthesis of EGF as well as EGF-R. Other markers of endoderm differentiation will be alphafetoprotein, transferrin, and basement membrane collagens. It is intended to study the first appearance and the distribution of EGF-R in mouse embryos using labeled EGF. Further studies of receptor distribution in differentiating EG cells will be made. The binding and molecular characteristics of EGF-R in various cells will be compared to find out if different forms exist. Antibodies to EGF will be prepared and used to study the synthesis of EGF by mouse embryonic tissues and in teratocarcinoma cells by immunological methods. Endogenous growth factors produced by EC cells will be sought. We hope to establish embryonic cell lines using EGF and other factors to stimulate growth.